Chemistry: A European Journal 2009-09-21

COMU: a safer and more effective replacement for benzotriazole-based uronium coupling reagents.

Ayman El-Faham, Ramon Subirós Funosas, Rafel Prohens, Fernando Albericio

Index: Chemistry 15 , 9404-9416, (2009)

Full Text: HTML

Abstract

We describe a new family of uronium-type coupling reagents that differ in their iminium moieties and leaving groups. The presence of the morpholino group in conjunction with an oxime derivative--especially ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma)--had a marked influence on the solubilities, stabilities, and reactivities of the reagents. Finally, the new uronium salt derived from Oxyma (COMU) performed extremely well in the presence of only 1 equiv of base, thereby confirming the effect of the hydrogen bond acceptor in the reaction. COMU also showed a less hazardous safety profile than the benzotriazole-based HDMA and HDMB, which exhibited unpredictable autocatalytic decompositions. Furthermore, the Oxyma moiety contained in COMU suggests a lower risk of explosion than in the case of the benzotriazole derivatives.